The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates

被引:41
|
作者
Ye, Gang [1 ,2 ]
Gallant, Joseph [3 ]
Zheng, Jian [4 ]
Massey, Christopher [5 ]
Shi, Ke [6 ]
Tai, Wanbo [7 ]
Odle, Abby [4 ]
Vickers, Molly [4 ]
Shang, Jian [1 ,2 ]
Wan, Yushun [1 ,2 ]
Du, Lanying [7 ]
Aihara, Hideki [6 ]
Perlman, Stanley [4 ]
LeBeau, Aaron [3 ]
Li, Fang [1 ,2 ]
机构
[1] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA
[2] Univ Minnesota, Ctr Coronavirus Res, St Paul, MN 55108 USA
[3] Univ Minnesota, Dept Pharmacol, 3-249 Millard Hall, Minneapolis, MN 55455 USA
[4] Univ Iowa, Dept Microbiol & Immunol, Iowa City, IA 52242 USA
[5] Univ Texas Med Branch, Inst Off Regulated Nonclin Studies, Galveston, TX 77555 USA
[6] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA
[7] New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Viral Immunol, New York, NY 10021 USA
来源
ELIFE | 2021年 / 10卷
基金
美国国家卫生研究院;
关键词
NEUTRALIZES SARS-COV-2; RECEPTOR; SPIKE; CORONAVIRUSES; MECHANISMS;
D O I
10.7554/eLife.64815
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking viral receptor angiotensin-converting enzyme 2 (ACE2). The lead drug candidate possessing an Fc tag (Nanosota-1C-Fc) bound to SARS-CoV-2 RBD similar to 3000 times more tightly than ACE2 did and inhibited SARS-CoV-2 pseudovirus similar to 160 times more efficiently than ACE2 did. Administered at a single dose, Nanosota-1C-Fc demonstrated preventive and therapeutic efficacy against live SARS-CoV-2 infection in both hamster and mouse models. Unlike conventional antibodies, Nanosota-1C-Fc was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of Nanosota-1C-Fc documented an excellent in vivo stability and a high tissue bioavailability. As effective and inexpensive drug candidates, Nanosota-1 may contribute to the battle against COVID-19.
引用
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页数:19
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